The pathogenesis of chronic obstructive lung disease (emphysema) will be investigated using mainly nitrogen oxides, generated in tobacco smoke and in the atmosphere, as well as ozone and other oxidizing gases. Rats of all ages will continue to be exposed for short and lifetime periods, continuously and intermittently, so that a threshold level may be identified and the pathogenesis of the chronic disease revealed. Quantitative methods are used in the various disciplines, clinical, physiological (in vivo and in vitro), hematological, morphological including pathology, electron microscopy, histochemistry, cell renewal rates, and oxidative biochemistry and enzymology. This study of the sequence of events resulting insidiously in dry, voluminous lungs with increased residual volumes and lost parenchymal (alveolar) tissue has been under way in a variety of orientations since 1962 in this laboratory.